Inhibitory Effects of Royal Jelly and Its Functional Components on the Proliferation of MKN-28 Gastric Cancer Cells.

Royal jelly (RJ) is a natural food product with nutritional value and anticancer activity. However, their effects on gastric cancer are unclear. Here, we show that treatment with 5-320 µg/mL of RJ, ethanol extract (RJEE), and protein hydrolyzate (RJPH) decreased the viability of MKN-28 gastric cancer cells, with a half-maximal inhibitory concentration of 123.22 µg/mL for RJEE. RJ, RJEE, and RJPH increase the lactate dehydrogenase release rate and change the morphology of the cells, resulting in cell shrinkage, nucleoplasm condensation, and the formation of apoptotic bodies. RJ and its functional components stagnated the cell cycle in the G0/G1 phase, accompanied by the accumulation of reactive oxygen species, decreased mitochondrial membrane potential, and increased expression levels of p53 and p21 proteins, caspase-3 activation, and apoptosis. Therefore, RJ, RJEE, and RJPH have potential inhibitory effects on the proliferation of gastric cancer cells.

Sea cucumber plasmalogen enhance lipophagy to alleviate abnormal lipid accumulation induced by high-fat diet.

Sea cucumber phospholipids, including the plasmalogen (PlsEtn) and plasmanylcholine (PakCho), have been shown to play a regulatory role in lipid metabolism disorders, but their mechanism of action remains unclear. Therefore, high-fat diet (HFD) and palmitic acid were used to establish lipid accumulation models in mice and HepG2 cells, respectively. Results showed that PlsEtn can reduce lipid deposition both in vivo and in vitro. HFD stimulation abnormally activated lipophagy through the phosphorylation of the AMPK/ULK1 pathway. The lipophagy flux monitor revealed abnormalities in the fusion stage of lipophagy. Of note, only PlsEtn stimulated the dynamic remodeling of the autophagosome membrane, which was indicated by the significantly decreased LC3 II/I ratio and p62 level. In all experiments, the effect of PlsEtn was significantly higher than that of PakCho. These findings elucidated the mechanism of PlsEtn in alleviating lipid accumulation, showed that it might be a lipophagy enhancer, and provided new insights into the high-value utilization of sea cucumber as an agricultural resource.

Docosahexaenoic Acid-Acylated Astaxanthin Monoester Ameliorates Amyloid-ß Pathology and Neuronal Damage by Restoring Autophagy in Alzheimer's Disease Models.

SCOPE: Astaxanthin (AST) is ubiquitous in aquatic foods and microorganisms. The study previously finds that docosahexaenoic acid-acylated AST monoester (AST-DHA) improves cognitive function in Alzheimer's disease (AD), although the underlying mechanism remains unclear. Moreover, autophagy is reportedly involved in amyloid-ß (Aß) clearance and AD pathogenesis. Therefore, this study aims to evaluate the preventive effect of AST-DHA and elucidates the mechanism of autophagy modulation in Aß pathology. METHODS AND RESULTS: In the cellular AD model, AST-DHA significantly reduces toxic Aß1-42 levels and alleviated the accumulation of autophagic markers (LC3II/I and p62) in Aß25-35 -induced SH-SY5Y cells. Notably, AST-DHA restores the autophagic flux in SH-SY5YmRFP-GFP-LC3 cells. In APP/PS1 mice, a 3-month dietary supplementation of AST-DHA exceeded free-astaxanthin (F-AST) capacity to increase hippocampal and cortical autophagy. Mechanistically, AST-DHA restores autophagy by activating the ULK1 signaling pathway and restoring autophagy-lysosome fusion. Moreover, AST-DHA relieves ROS production and mitochondrial stress affecting autophagy in AD. As a favorable outcome of restored autophagy, AST-DHA mitigates cerebral Aß and p-Tau deposition, ultimately improving neuronal function. CONCLUSION: The findings demonstrate that AST-DHA can rectify autophagic impairment in AD, and confer neuroprotection in Aß-related pathology, which supports the future application of AST as an autophagic inducer for maintaining brain health.

Antioxidants ameliorate oxidative stress in alcoholic liver injury by modulating lipid metabolism and phospholipid homeostasis.

Alcoholic liver disease (ALD) is a significant risk factor in the global disease burden. The antioxidants vitamin C (Vc) and N-acetyl cysteine (NAC) have shown hepatoprotective effects in preventing and treating ALD. However, the correlation between the improved effect of antioxidants and lipid metabolism is still unclear. In this study, AML12 cells and C57BL/6 mice stimulated with alcohol were used to investigate the protective effects and potential mechanisms of two antioxidants (Vc and NAC) on alcoholic liver injury. Results showed that Vc and NAC attenuated intracellular lipid accumulation and oxidative damage induced by excessive alcohol exposure in hepatic AML12 cells. The in vivo results indicated that antioxidants ameliorated alcohol-induced changes in histopathology, reducing the levels of alcohol metabolizing factors and aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), and total cholesterol (TC) contents, which demonstrated that antioxidants effectively mitigated liver injury in ALD mice. Further studies showed that antioxidants reversed the disruption of fatty acid (FA) synthesis and lipid transport induced by alcohol exposure, and restored phospholipid levels. Especially, Vc and NAC increased the endogenous antioxidant plasmenyl phosphatidylethanolamine (PlsEtn). Additionally, antioxidants ameliorated the alcohol-impaired mitochondrial function and inhibited excessive oxidative stress. In conclusion, antioxidants can regulate lipid metabolism and phospholipid homeostasis, which in turn inhibit oxidative stress and thereby exert protective effects against ALD.

Study on the hypolipidemic activity of rapeseed protein-derived peptides.

Hyperlipidaemia, a common chronic disease, is the cause of cardiovascular diseases such as myocardial infarction and atherosclerosis. Generally, drugs for lowering blood lipids have disadvantages such as short or poor efficacy, high toxicity, and side effects. Rapeseed active peptides are excellent substitutes for lipid-lowering drugs because of their high biological safety, strong penetration, and easy absorption by the human body. This study separated and purified the rapeseed peptides using gel chromatography and mass spectrometry. Rapeseed peptides amino acid sequences were determined to obtain Glu-Phe-Leu-Glu-Leu-Leu (EFLELL) peptides with good hypolipidaemic activity and IC50 values of 0.1973 ± 0.05 mM (sodium taurocholate), 0.375 ± 0.03 mM (sodium cholate), and 0.203 ± 0.06 mM (sodium glycine cholate). The EFLELL hypolipidaemic activity was evaluated, and its mechanism of action was investigated using cell lines. Rapeseed peptide treatment significantly decreased the total cholesterol (T-CHO), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, and the protein and gene expression levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein cholesterol (LDLR) suggested the mechanism. Molecular docking revealed that the binding energy between rapeseed peptide and LDLR-PCSK9 molecules was -6.3 kcal/mol and -8.1 kcal/mol. In conclusion, the rapeseed peptide EFLELL exerts a favourable hypolipidaemic effect by modulating the LDLR-PCSK9 signalling pathway.

Sepsis-related immunosuppression: a bibliometric analysis.

Background: Sepsis is one of the main causes of death in critically ill patients. Immunosuppression was involved deeply in the process of sepsis. The status of research on sepsis-related immunosuppression remains unclear. In this study, a bibliometric analysis was conducted to provide a preliminarily analysis of the current research status in sepsis-related immunosuppression. Methods: The Science Citation Index Expanded (SCI-E) database in the Web of Science Core Collection was used as the data source for the literature search, and the time was set from the inception of the database to the last retrieval time for this study (i.e., May 21, 2022). Using the topic search, we searched for "sepsis" and then for "immunosuppression" in the results to obtain the final results. On the search page of the SCI-E database, we selected the document type, topic direction, MeSH topic heading, MeSH qualifier, keywords, author, journal, country, research institution, language, etc., to obtain the distribution results, and manually removed any duplicate records. We analyzed the use of keywords in the literature and the centrality of the authors, countries, and research institutions. Results: A total of 4,132 articles were retrieved from the database over the search period of 1900 to May 21, 2022. The number of articles published increased annually. A trend of rapid growth was also observed in the number of citations. The most common topic words were humans, male, and female. The most used keywords were sepsis, immunosuppression, and male. The most published researcher was Monneret from Lyon, France. The authors of the article mainly specialized in immunology and surgery. Moldawer and Chaudry from the United States (US) had engaged in the most collaborations with other researchers. The journals that publish literature in this field are mainly journals related to critical care medicine, and the core journals included Shock, Critical Care, and Critical Care Medicine. Conclusions: More and more studies are being published on sepsis-related immunosuppression and largely being conducted in developed countries. Chinese researchers need to carry out more collaborative research.

Co-encapsulation of rutinoside and ß-carotene in liposomes modified by rhamnolipid: Antioxidant activity, antibacterial activity, storage stability, and in vitro gastrointestinal digestion.

The surfactant rhamnolipid (RL) was used to modify the liposomes. ß-carotene (ßC) and rutinoside (Rts) were utilized to generate co-encapsulated liposomes through an ethanol injection method that used both hydrophilic and hydrophobic cavities to fabricate a novel cholesterol-free composite delivery system. The RL complex-liposomes loaded with ßC and Rts (RL-ßC-Rts) showed higher loading efficiency and good physicochemical properties (size = 167.48 nm, zeta-potential = -5.71 mV, and polydispersity index = 0.23). Compared with other samples, the RL-ßC-Rts showed better antioxidant activities and antibacterial ability. Moreover, dependable stability was uncovered in RL-ßC-Rts with still 85.2% of ßC storage from nanoliposome after 30 days at 4°C. Furthermore, in simulated gastrointestinal digestion, ßC exhibited good release kinetic properties. The present study demonstrated that liposomes constructed from RLs offer a promising avenue for the design of multicomponent nutrient delivery systems using both hydrophilic.

Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C.

This study investigated the effect of combined thymosin α1 and vitamin C (Tα1 + VitC) on the immunological responses of septic rats. Five groups were designed. The septic model was established by the cecal ligation puncture (CLP) method. The sham group did not undergo CLP, the model group was given normal saline solution, the Tα1 group was given Tα1 (200 µg/kg), the VitC group was given VitC (200 mg/kg), and the Tα1 + VitC group was given Tα1 + VitC. Specimens for immunological analyses were collected at 6, 12, 24, and 48 h posttreatment in each group except for the sham group (only at 48 h). CD4 + CD25 + T cells in the peripheral blood and dendritic cell (DC) proportions in the spleen were analyzed by flow cytometry. Tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), transforming growth factor-ß (TGF-ß1), and nuclear factor kappa-B (NF-κB) were measured by ELISA. CD4 + CD25 + T cells and OX62 + DCs levels significantly increased in the model group and decreased in the Tα1 and/or VitC treatment groups. Similarly, the levels of TNF-α, IL-6, TGF-ß1, and NF-κB significantly increased in the model group and decreased in the Tα1, VitC, and Tα1 + VitC groups, indicating that combined Tα1 and VitC therapy may help regulate the immunological state of patients with sepsis, thereby improving prognosis.

The novel biomarker circ_0020339 drives septic acute kidney injury by targeting miR-17-5p/IPMK axis.

PURPOSE: Sepsis is a systemic life-threatening inflammatory disease, which leads to septic acute kidney injury (AKI). Circular RNAs (circRNAs) are involved in septic AKI. Herein, we aimed to expound the action of circ_0020339 in septic AKI. The dysregulation of plasma circRNAs between patients with septic non-AKI and patients with septic AKI were screened by circRNA chip. METHODS: The dysregulation of circ_0020339, microRNA (miR)-17-5p, and inositol polyphosphate multi kinase (IPMK) mRNA was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability and apoptosis were measured by cell counting kit-8 (CCK-8) and flow cytometry, respectively. The release of serum creatinine (SCr), tissue inhibitor metalloproteinase-2 (TIMP-2), insulin-like growth factor binding protein-7 (IGFBP7), tumor necrosis factor (TNF)α and interleukin (IL)-1ß was evaluated by enzyme-linked immunosorbent assay (ELISA). Bioinformatic analysis, dual-luciferase reporter assay and miRNA pull down assay were used to confirm the interaction between miR-17-5p and circ_0020339 or IPMK 3'untranslated region (UTR). Protein level of IPMK, TNF receptor-associated factor 6 (TRAF6), phosphorylated AKT (p-AKT)/total (t)-AKT, p-nuclear factor kappa-B (NF-κB) kinase (p-IKK)/t-IKK, p-inhibitor of NF-κB (p-IκB)α/t-IκBα, and p-p65/t-p65 were conducted by western blot. RESULTS: Circ_0020339 was upregulated in the plasma of patients with septic AKI as well as LPS-treated HK2 cells and C57BL/6 mice relative to the corresponding counterparts. Functionally, circ_0020339 was positively correlated with markers of renal functional injury and inflammation in patients with septic AKI; si-circ_0020339 facilitated cell proliferation, while restrained cell apoptosis and inflammation in LPS-triggered HK2 cells; meanwhile, si-circ_0020339 restrained survival rate, renal functional injury and inflammation in LPS-triggered C57BL/6 mice. Furthermore, circ_0020339 and IPMK 3'UTR shared the same complementary sites with miR-17-5p. CONCLUSION: si-circ_0020339 attenuated LPS-induced cell damage by targeting miR-17-5p/IPMK axis and inactivation of TRAF6/p-AKT/p-IKK/p-IκBα/p-p65. Altogether, plasma circ_0020339 serves as a novel diagnostic marker of patients with septic AKI.

Rapeseed peptide inhibits HepG2 cell proliferation by regulating the mitochondrial and P53 signaling pathways.

BACKGROUND: Rapeseed peptide, extracted from rapeseed protein, is known to have a variety of biological activities. In this study, the anti-proliferation effect and molecular mechanism of rapeseed peptide on HepG2 cells were investigated. RESULTS: In vitro anticancer experiments showed that the rapeseed peptide NDGNQPL could inhibit HepG2 cell proliferation in a concentration-dependent manner [half maximal inhibitory concentration (IC50 ), 1.56 mmol L-1 ). HepG2 cells were induced by NDGNQPL at a 0.5 mmol L-1 concentration and exhibited a 28.39 ± 0.80% apoptosis rate and a cell cycle arrest in the G0/G1 phase. Meanwhile, rapeseed peptide induced a decrease in mitochondrial membrane potential, an increase in reactive oxygen species (ROS) release, and changes in the nuclear morphology of HepG2 cells, indicating that rapeseed peptide could induce cell apoptosis through the mitochondrial pathway. In addition, rapeseed peptide activated the proliferation-related P53 signaling pathway, in which the expression levels of P53, P21, and cleaved-caspase3 were up-regulated, while the expression levels of murine double minute 2 (MDM2) were down-regulated. In molecular docking simulations, NDGNQPL exhibited a good affinity for the MDM2 molecule, which supported the notion that the rapeseed peptide is able to inhibit MDM2, a negative regulator of P53. CONCLUSION: The current results indicate that the rapeseed-derived NDGNQPL peptide has the potential to inhibit the proliferation of HepG2 cells and promote human health. © 2022 Society of Chemical Industry.

Sea cucumber ether-phospholipids improve hepatic steatosis and enhance hypothalamic autophagy in high-fat diet-fed mice.

As a promising group of natural bioactive lipids, ether-phospholipids (ether-PLs), exhibit the ability to attenuate high-fat diet (HFD)-induced lipid accumulation and atherosclerosis. However, the underlying mechanism is unclear. Autophagy has been implicated in the regulation of obesity. Therefore, we investigated the effects of dietary ether-PLs on hepatic steatosis and the activation of hypothalamic autophagy. HFD-fed C57BL/6J mice were orally administered with ether-PLs (150 mg/kg body weight) including plasmenyl phosphatidylethanolamine (PE-P) and plasmanyl phosphatidylcholine (PC-O) for three days or eight weeks. Ether-PLs supplementation relieved diet-induced hepatic lipid accumulation and regulated the hypothalamic peroxisome proliferator-activated receptor gamma (PPARγ) and CD36. Notably, PE-P activated hypothalamic autophagy more strongly than PC-O, with an increased ratio of microtubule-associated protein light chain 3 II/I (LC3II/I) and reduced p62/sequestosome-1 (p62) accumulation by rescuing the HFD-impaired autophagy-lysosome fusion. The phosphorylation of ULK1 mediated by Akt-mTOR and AMPK, was involved in ether-PLs activated autophagy. Furthermore, the enhanced hypothalamic autophagy promoted the production of α-melanocyte-stimulating hormone (α-MSH), which has been reported to maintain energy balance. It is concluded that ether-PLs ameliorated HFD-induced hypothalamic autophagy and ameliorated hepatic steatosis. Ether-PLs could thus be an attractive autophagy-enhancers against chronic HFD-induced obesity.

Anti-inflammatory activity of peptides derived from millet bran in vitro and in vivo.

Various food-derived bioactive peptides have been found with potential anti-inflammatory effects. Millet bran peptide is a food-derived bioactive peptide extracted from millet bran, a by-product of millet processing. In this study, the anti-inflammatory effect of millet bran peptides was investigated. A lipopolysaccharide (LPS)-induced RAW264.7 cell and an animal experiment model were established to test the anti-inflammatory activity of millet bran peptides in vitro. As indicated by the results, millet bran peptides could significantly reduce the levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and prostaglandin E2 (PGE2), in the LPS-induced RAW264.7 cell. As demonstrated by the animal experiment results, millet bran peptides could mitigate the inflammation of spontaneously hypertensive rats (SHRs). According to the western blotting results, millet bran peptides reduced the phosphorylation level of an extracellular signal-related kinase (ERK), I Kappa B (IKB), p65, and p38 of LPS-induced RAW264.7 cells. As indicated by 16S rDNA sequencing analysis results, millet bran peptides could modify the composition of intestinal microbes. In brief, millet bran peptides could have anti-inflammatory activities in vivo and in vitro and mitigate the inflammation of LPS-induced RAW264.7 cells by regulating the signaling pathways of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK). The above research has laid a theoretical basis for the application of plant-derived peptides in health food.

Oral delivery of decanoic acid conjugated plant protein shell incorporating hybrid nanosystem leverage intestinal absorption of polyphenols.

Polyphenols are potent antioxidants, but their poor oral bioavailability owing to intrinsic insolubility and low permeability significantly hampers their effectiveness for clinical translation. Herein, upper intestinal absorptive polymer-lipid hybrid nanoparticles (PLN) was designed by exploiting the lipidic core for drug encapsulation and the decanoic acid conjugated rapeseed protein as the biopolymeric shell for gastrointestinal stability, retention and permeability. Polyphenol ellagic acid loaded core-shell PLN (EA-PLN(C/S)) was characterized of favorable physicochemical properties in simulated gastric- and intestinal fluids, including high drug loading capacity, slow drug release and prolonged stability. In Caco-2 monolayers, the cellular transport of EA-PLN(C/S) involved dual-paracellular and endocytosis pathways. Compared to drug in suspension or lipidic core nanoparticles, orally administered EA-PLN(C/S) was retained longer and more permeable via the duodenum and jejunum of upper intestine, resulting in up to 5.3-fold and 1.4-fold enhancement in the extent of drug absorption and colonic accumulation, respectively. In an acute colitis murine model, EA-PLN(C/S) at 6 mg/kg low dose markedly reduced colonic lipid peroxidation in contrast to no antioxidant effect in other EA formulations. This work suggests that integration of engineered plant protein biopolymer with lipid nanoparticles created unique oral drug delivery systems enabling intestinal site-specific absorption for effective antioxidant therapeutics.

RIPK1 dephosphorylation and kinase activation by PPP1R3G/PP1γ promote apoptosis and necroptosis.

Receptor-interacting protein kinase 1 (RIPK1) is a key regulator of inflammation and cell death. Many sites on RIPK1, including serine 25, are phosphorylated to inhibit its kinase activity and cell death. How these inhibitory phosphorylation sites are dephosphorylated is poorly understood. Using a sensitized CRISPR whole-genome knockout screen, we discover that protein phosphatase 1 regulatory subunit 3G (PPP1R3G) is required for RIPK1-dependent apoptosis and type I necroptosis. Mechanistically, PPP1R3G recruits its catalytic subunit protein phosphatase 1 gamma (PP1γ) to complex I to remove inhibitory phosphorylations of RIPK1. A PPP1R3G mutant which does not bind PP1γ fails to rescue RIPK1 activation and cell death. Furthermore, chemical prevention of RIPK1 inhibitory phosphorylations or mutation of serine 25 of RIPK1 to alanine largely restores cell death in PPP1R3G-knockout cells. Finally, Ppp1r3g-/- mice are protected from tumor necrosis factor-induced systemic inflammatory response syndrome, confirming the important role of PPP1R3G in regulating apoptosis and necroptosis in vivo.

USP13-mediated IRAK4 deubiquitination disrupts the pathological symptoms of lipopolysaccharides-induced sepsis.

Ubiquitin-specific peptidase 13 (USP13) has been reported to participate in tumorigenesis, cell cycle arrest, endoplasmic reticulum-associated degradation, and immune responses. Here, we explored the function of USP13 in pro-inflammatory cytokine production of macrophages and its role in mouse sepsis model. Primary bone-marrow-derived macrophages (BMDMs) isolated from wild type (WT) and USP13MKO mice were treated by lipopolysaccharides (LPS), IL-4, toll-like receptors (TLRs) agonists, and IRAK4 inhibitor to profile the inflammatory responses with different genotypes. Mouse sepsis model (WT and USP13MKO) created by intraperitoneal injection with LPS plus d-galactosamine was used to assess septic shock-induced survival and lung inflammation. Flow cytometry, qRT-PCT, Western blot, and ELISA were performed to detect pro-inflammatory production and macrophage polarization. USP13 was a key regulator of IRAK4 deubiquitination in BMDMs and its myeloid specific deficiency contributed to LPS-induced pro-inflammatory response and septic symptoms. IRAK4 inhibitor co-administration improved in LPS-induced inflammatory responses in both BMDMs and septic mice. USP13 negatively regulates LPS-induced sepsis shock by targeting IRAK4. In summary, targeting USP13-IRAK4 axis might be a potential therapeutic strategy for the treatment of inflammation in sepsis shock.

Study of monoglycerides enriched with unsaturated fatty acids at sn-2 position as oleogelators for oleogel preparation.

The effect of using highly unsaturated 2-monoglycerides as oleogelators on the properties of soybean oil oleogels designed to eliminate saturated and trans fatty acids was investigated in this study. We adopted a novel two-step synthesis aiming to increase the yield of the 2-monoglycerides. The optimal synthesis conditions were a substrate weight ratio of 2:1 (w/w), 10% Lipozyme 435 (w/w total reactants), and 4 h of reaction time at room temperature. Under these conditions, the 2-monoglyceride yield (40.69%) increased by 10% compared to that of the conventional synthesis route. Additionally, soybean oil oleogels prepared using 10% 2-monoglycerides with or without rice bran wax were systematically characterized by polarized light microscopy, a texture analyzer, XRD spectroscopy, and rheometry. Comparative studies indicated that a combination of rice bran wax and 2-monoglycerides had synergistic effects on gel properties. A mixture of 4% rice bran wax and 6% 2-monoglycerides was found to provide better oleogels.

HSP70 promotes MLKL polymerization and necroptosis.

Mixed lineage kinase domain-like protein (MLKL) is the proposed executioner of necroptosis. Our recent findings identify a novel inhibitor necroptosis-blocking compound 1 (NBC1) which specifically conjugates to two cysteines of heat shock protein 70 (HSP70) to block its function. Importantly, HSP70 promotes MLKL polymerization to activate necroptosis.

Rice bran attenuated obesity via alleviating dyslipidemia, browning of white adipocytes and modulating gut microbiota in high-fat diet-induced obese mice.

Obesity has become an international public health problem. In this study, an obese mice diet was supplemented with raw rice bran (RRB) or infrared radiation-stabilized rice bran (IRRB) to investigate the attenuation of obesity induced by a high-fat diet. Mice were fed a normal diet or a high-fat diet with and without rice bran supplementation (300 mg per kg body weight per day) by oral gavage for 39 days to investigate the obesity preventive effect. The results indicate that different rice bran supplements reduced body weight, relative adipose tissue weight, inflammation, and serum parameters, and relieve liver steatosis to varying degrees. The data of real-time qPCR and western blots (WB) showed that rice bran activated brown adipose tissue (BAT) and increased white adipose tissue (WAT) browning. Rice bran also reduced the ratio of Firmicutes/Bacteroidetes and enhanced the relative abundance of Akkermansia. In summary, our findings suggest that rice bran intervention played a significant role in reducing dyslipidemia, alleviating inflammation, enhancing thermogenesis and modulating gut microbiota for the prevention and control of obesity.

Necroptosis-blocking compound NBC1 targets heat shock protein 70 to inhibit MLKL polymerization and necroptosis.

Necroptosis is a regulated necrotic cell death pathway involved in development and disease. Its signaling cascade results in the formation of disulfide bond-dependent amyloid-like polymers of mixed lineage kinase domain-like protein (MLKL), which mediate proinflammatory cell membrane disruption. We screened compound libraries provided by the National Cancer Institute and identified a small-molecule inhibitor of necroptosis named necroptosis-blocking compound 1 (NBC1). Biotin-labeled NBC1 specifically conjugates to heat shock protein Hsp70. NBC1 and PES-Cl, a known Hsp70 substrate-binding inhibitor, block the formation of MLKL polymers, but not MLKL tetramers in necroptosis-induced cells. In vitro, recombinant Hsp70 interacts with the N-terminal domain (NTD) of MLKL and promotes NTD polymerization, which has been shown to mediate the cell killing activity. Furthermore, the substrate-binding domain (SBD) of Hsp70 is sufficient to promote MLKL polymerization. NBC1 covalently conjugates cysteine 574 and cysteine 603 of the SBD to block its function. In addition, an SBD mutant with both cysteines mutated to serines loses its ability to promote MLKL polymerization. Interestingly, knockdown of Hsp70 in cells leads to MLKL destabilization, suggesting that MLKL might also be a client protein of Hsp70. In summary, using NBC1, an inhibitor of necroptosis, we identified Hsp70 as a molecular chaperone performing dual functions in necroptosis. It stabilizes MLKL protein under normal condition and promotes MLKL polymerization through its substrate-binding domain during necroptosis.

Atmospheric Corrosion Analysis and Rust Evolution Research of Q235 Carbon Steel at Different Exposure Stages in Chengdu Atmospheric Environment of China.

In order to effectively reduce and retard corrosion of the power transmission and transformation equipment in Chengdu power grid and to improve power supply reliability, Q235 carbon steel material which is the most widely used metal material in power grid was selected as the targeted research object in this article. Exposure experiments were performed in urban atmospheric environment of Chengdu city in the southwest region of China. The corrosion behavior of Q235 carbon steel material was investigated at different seasons. The macro- and micromorphologies after corrosion were observed using a digital camera and scanning electron microscopy (SEM), respectively. Element distribution of the rust layer and the corrosion products was characterized by energy-dispersive spectroscopy (EDS), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR); the corrosion mechanism was also briefly analyzed.